1. Field of the Invention
This invention relates to antimicrobial formulations for providing antimicrobial effectiveness to the skin without irritation or dryness. The formulations, comprising parachlorometaxylenol, are particularly useful in the health care profession such as in surgical practice as a pre-operative scrub.
2. Description of Related Art
Effective antiseptic or disinfectant compositions can be formed by combining a surfactant or detergent with an antimicrobial agent. Thus, antiseptic cleaning compounds can be formulated rather easily; however, many such compositions are not suitable for use in contact with human skin due to the abrasive nature of the surfactant-containing composition, and there are surfactants incompatible with many antimicrobial agents.
Where the composition is intended for use as surgical scrub, mildness is an important consideration. Mildness indicates the composition does not cause excessive irritation of the skin, such as erythema.
In a majority of cases, skin irritation can be attributed to contact of the skin with a surfactant. It is believed that skin irritation results partly due to the nature of the surfactant itself and, in part, due to the action of the surfactant in weakening the resistance of the skin. The degree of irritation may vary significantly with the surfactant, the individual user, the length of contact and the conditions of contact. In many cases the degree of irritation is also affected by the combination of the antimicrobial agent and the surfactant.
It is believed that surfactants have a denaturing effect on the skin. Thus, antimicrobial agents or chemicals which normally do not irritate the skin when combined with a surfactant can penetrate or be readily absorbed by the skin and cause irritation. The absorption of antimicrobial agents or chemicals by the skin is generally undesirable.
Surgical scrub procedures and techniques are highly conducive to the development of erythema and other irritations. All personnel involved in surgical procedures use a surgical scrub in preparation for surgery. Frequently, the same individual will scrub three to five times on a single day. A typical surgical scrub involves placing a cleansing composition on the hand. Commonly, a brush or sponge is used and the arms from the elbows to the fingertips are scrubbed thoroughly for as long as ten minutes. Thus, the epidermal layers of the skin are subject to significant rubbing and aggravation. After the arms and hands have been scrubbed they are rinsed, dried and placed into rubber gloves. The rinse is often not complete and residual surfactant and/or antimicrobial compounds from the cleansing composition are left on the skin. Many times, the hands remain gloved for as long as six hours. During this time the hand perspires and the pores can open and enlarge, thereby allowing residual surfactants and/or antimicrobial compounds to penetrate the skin. This in turn can create topical skin irritations. The likelihood of irritation or erythema increases with the frequency one performs the surgical scrub procedure. It is important that surgical scrub compositions be very mild, but yet effective.
Numerous attempts have been made to develop formulations containing antimicrobial agents and surfactants, which reduce or eliminate skin irritation and provide effective antiseptic or disinfectant properties. However, the efficacy of antiseptic or disinfectant compositions is greatly influenced by a number of variables, including pH, temperature, concentration of organisms, duration of exposure, concentration of the antiseptic and the type of surfactants used in the formulation.
Formulations containing the antimicrobial agent, chlorhexidine, have been used as antibacterial skin cleaners in surgical scrubs. Formulations containing chlorhexidine generally include a surfactant and a low percentage of an alcohol such as isopropanol.
Billany et al., U.S. Pat. No. 3,960,745, discloses a chlorhexidine cleansing composition formulated with a polyoxyethylene-polyoxypropylene nonionic surfactant. The formulation is commercially available as HIBICLENS.RTM. (trademark of ICI Americas, Inc.) sold by Stuart Pharmaceuticals, Wilmington, Del. Billany et al. discloses that anionic surfactants are not desirable surfactants because they may destroy the antibacterial activity of chlorhexidine solutions by complexing with the cationic chlorhexidine. Cationic surfactants are also not desirable because of their irritancy, and because, in combination with a soluble chlorhexidine salt, double decomposition can occur with the formation of insoluble chlorhexidine salts and consequent loss of antibacterial activity. Equally unsuitable surfactants for use in such formulations are amphoteric surfactants, which contain either anionic or cationic centers, depending upon pH, and they suffer from the above-described disadvantages of anionic and cationic surfactants.
Other formulations have used bisbiguanide as an antimicrobial agent as disclosed in U.S. Pat. No. 4,456,543 to Ownes. Ownes discloses an antibacterial cleansing formulation containing bisbiguanide and one or more nonionic polyoxyalkylene surfactants.
Dewar et al., U.S. Pat. No. 4,157,977 discloses surfactant-germicide compositions containing an antimicrobial active phenolic derivative in combination with hydroxyacetic acid and a surfactant.
Casey et al., U.S. Pat. No. 4,252,665 discloses a disinfectant cleaning composition containing ortho-benyzl-para-chlorophenol, anionic surfactants and sulfobetaine surfactants.
Langguth et al., U.S. Pat. No. 4,257,907 discloses disinfectant cleaning compositions containing ortho-benzyl-para-chlorophenol, sulfobetaine surfactants and anionic surfactants.
White, European Patent Application 0 223 681, discloses an alcohol-based antimicrobial composition.
Meldovanyl et al., United Kingdom Application 2 203 339, discloses a microbicidal formulation containing antimicrobial agents and surfactants.
Formulations containing the antimicrobial agent parachlorometaxylenol (PCMX) have been developed as disclosed in U.S. Pat. No. 4,632,772 to Garabedian et al. Garabedian et al. discloses an antimicrobial composition containing the active antimicrobial agent PCMX and an ionic surfactant, alkyl aryl ethoxylated sulfonate.
Melvin, U.S. Pat. No. 3,326,808 discloses an antiseptic surfactant composition containing PCMX and an anionic surfactant, the sodium salt of 2-sulfomethyl myristate.
PCMX, being phenolic in nature with acidic hydrogen and insoluble in water, reacts with bases to form salts: ##STR1##
PCMX exists in the salt form in solutions at higher pH and in the phenolic state at lower pH. Therefore, efficacy of the PCMX formulation is greatly influenced by pH. The efficacy of PCMX is also compromised by other factors such as solubility and the formation of an association complex with other components in a formulation.
PCMX is related to other phenolic compounds such as cresol, carbolic acid, and hexachlorophene and has a characteristic phenolic odor. Other names for PCMX include chloroxylenol; 4-chloro-3, 5-xylenol; 4-chloro-3,5-dimethylphenol, 2-chloro-m-xylenol; 2-chloro-5-hydroxy-m-xylene; 2-5-hydroxy-m-xylene; 2-chloro-5-hydroxy-1,3-dimethylbenzene; 4-chlor-1-hydroxy-3, 5-dimethyl benzene; and 3,5-dimethyl-4-chlorophenol.
PCMX is a desirable antimicrobial agent having sixty times the antimicrobial activity of other phenolics against a variety of gram-positive and gram-negative bacteria as reported by Windholz, M(ed). The Merck Index: An Encyclopedia of Chemicals and Drugs, ed 9. Rahway, N.J., Merck and Co., 1976. However, as reported by Ray et al., "Microbiological Evaluation of PCMX Complexes." J. Pharmacol Sci. 57:609-613 (1968), PCMX will react with various nonionic macromolecules such as polyethylene glycol, methyl-cellulose and polysorbate to form association complexes and therefore diminish the inhibiting and bactericidal activity of PCMX.
Furthermore, as disclosed in U.S. Pat. No. 4,326,977 to Schmolka, the efficacy of antiseptic compositions may be influenced by the type of surfactants used because some surfactants are incompatible with many antiseptic agents.
Therefore, due to the antimicrobial activity of PCMX, it is desirable to have a PCMX formulation which provides substantially maximized efficacy and does not promote dryness or irritation to the skin. However, such a formulation is difficult to produce due to the incompatibility of many surfactants with many antiseptic agents like PCMX.